The intrinsic instability of peptides limits their potential as reagents in molecular biology and drug discovery. Nonpeptidic scaffolds that adopt well-defined conformations and display protein-like side chains would be invaluable alternatives to peptides (Yin & Hamilton, Angew. Chem. Int. Ed. 44:4130-4163 (2005); Gellman, Acc. Chem. Res. 31:173-180 (1998)). Biomimetic oligomers (Gellman, Acc. Chem. Res. 31:173-180 (1998); Sanford et al., Eur. J Biochem. 271:1416-1425 (2004); Hill et al., Chem. Rev. 101:3893-4011 (2001); Barron & Zuckermann, Curr. Opin. Chem. Biol. 3:681-687 (1999); Stigers et al., Curr. Opin. Chem. Biol. 3:714-723 (1999)), such as β-peptides (Cheng et al., Chem. Rev. 101:3219-3232 (2001); Seebach & Matthews, Chem. Commun. 2015-2022 (1997)), have been intensively studied because they possess a high propensity to adopt defined secondary structures and resist degradation by proteolytic enzymes. These oligomers also retain perhaps the most important asset offered by peptides, namely access to a diverse set of side chain functional groups needed for molecular recognition and catalysis. Several nonpeptidic oligomers composed of carbamates, sulfonamides, ureas, hydrazino acids, aminoxy acids, anthranilamides, oligophenylacetylenes, and pyrrolinones, among others, have been described (U.S. Patent Application Publication No. US 2004/0116654 A1 to Gellman et al.; Gellman, Acc. Chem. Res. 31:173-180 (1998); Sanford et al., Eur. J. Biochem. 271:1416-1425 (2004); Hill et al., Chem. Rev. 101:3893-4011 (2001); Barron & Zuckermann, Curr. Opin. Chem. Biol. 3:681-687 (1999); Stigers et al., Curr. Opin. Chem. Biol. 3:714-723 (1999)). However, some of these oligomers lack peptide main chirality or amino acid side chains, thus limiting their ability to be used as peptide mimics. Thus, there remains a need for identifying a general method for the synthesis of distinctly folded, nonpeptidic oligomers in which the amide bond is replaced by aromatic rings yet the chiral main-chain and amino acid side chains are maintained.
The present invention is directed to overcoming these and other deficiencies in the art.